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Objective Radiotherapy modalities such as iodine-125 (I125) and ruthenium-106 (Ru106) brachytherapy and proton beam radiotherapy (PBR) are well established for the treatment of choroidal melanoma. This study aimed to evaluate the rates of local tumour control, globe retention and visual acuity (VA) outcomes in patients with choroidal melanoma treated with I125 or Ru106 brachytherapy or PBR.Methods and analysis A review was conducted of all cases of choroidal melanoma treated with Ru106 or I125 brachytherapy or PBR over a 10-year period. Patient demographics, comorbidities, tumour characteristics, treatment parameters and VA outcomes were analysed. A predictive nomogram was developed to estimate final VA based on baseline clinical, tumour and radiation parameters.Results A total of 310 eyes from 310 patients were included, comprising 175 patients (56.5%) treated with Ru106, 72 (23.2%) treated with I125 brachytherapy and 63 (20.3%) treated with PBR. Local tumour control was achieved in 95.8% of cases. The recurrence rates were 4.0%, 4.2% and 4.8% for Ru106, I125 and PBR, respectively. Retention rates were 96.0% for Ru106, 94.4% for I125 and 95.2% for PBR. LogMAR VA of 1.0 or better was maintained in 50.9% of Ru106patients, 27.8% of I125patients and 39.7% of those treated with PBR. Baseline LogMAR VA, tumour volume, radiation dose to the fovea, radiotherapy modality and follow-up duration were significant predictors of final VA and were incorporated into the nomogram.Conclusions Each radiotherapy modality demonstrated high rates of local tumour control and globe retention. The predictive nomogram may serve as a practical tool to support individualised visual prognostication and patient counselling in the management of choroidal melanoma.
Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system (CNS). Segmental denervation has been rarely reported in NMOSD resulting from severe myelitis leading to anterior horn cell loss or inflammatory myeloradiculitis. A 21-year-old woman presented due to lower limb dysesthesias evolving to paraparesis and sphincter disorders over a month. Electromyographic examination revealed acute denervation in L5/S1-innervated muscles with normal peripheral nerve conduction, pointing to anterior horn affection. Magnetic resonance imaging (MRI) showed a lesion at the level of T8-T9 in the thoracic spine and hypothalami. Serum aquaporin-4 antibody and cerebrospinal fluid (CSF) oligoclonal IgG bands were positive. The patient improved with intravenous methylprednisolone within 2 weeks. Overlapping inflammation of the central and peripheral nervous system can occur in NMOSD. Electromyography could be a helpful diagnostic tool in selected cases of NMOSD in the early diagnostic process, especially in patients with normal MRI findings.
Extended-release, once-nightly sodium oxybate (ON-SXB; LUMRYZ™) eliminates the middle-of-the-night dosing required with immediate-release, twice-nightly oxybates (TN-OXBs). RESTORE (NCT04451668) was an open label/switch study that assessed the safety and tolerability of ON-SXB in people with narcolepsy. Participants with narcolepsy aged ≥16 years who had completed the phase 3 REST-ON trial, were on stable-dose TN-OXB (switch participants), or were oxybate-naïve were eligible. For switch participants, initial ON-SXB doses were equivalent or closest to their prior total nightly TN-OXB dose. Doses could be titrated at ±1.5g/week until stable dosing was achieved (minimum, 4.5g/night; maximum, 9g/night). Treatment-emergent adverse events (TEAEs) during the 8-week dose titration period were recorded weekly for switch participants in the safety population (ie, received ≥1 ON-SXB dose) who completed a nocturnal AE questionnaire. Safety data were collected for 99.2% (129/130) of switch participants. All TEAEs reported by ≥3% of switch participants occurred during weeks 1-3; no TEAEs ≥3% were reported during weeks 4-8. At week 1, TEAEs ≥3% included nausea (3.2%), vomiting (3.2%), decreased appetite (3.2%), and urinary retention (3.2%) with the 6-g dose, and headache (7.0%) and somnolence (4.7%) with 9g. At week 2, TEAEs ≥3% included nausea (3.2%), upper respiratory infection (3.2%), dizziness (3.2%), and hypertension (3.2%) with 6g. At week 3, TEAEs ≥3% included vomiting (3.2%), enuresis (3.2%), insomnia (3.2%), and somnambulism (3.2%) with 6g. No TEAEs ≥3% were reported with 4.5g during weeks 1-3, or with 7.5g or 9g during weeks 2-3. Most TEAEs were mild or moderate in severity. The only reported severe TEAE was dyskinesia (1.2%) with the 7.5-g dose. During the ≥3-year RESTORE study, only 5.4% of switch participants discontinued ON-SXB due to a TEAE. For participants switching from stable-dose TN-OXB, ON-SXB was well tolerated during the 8-week titration period, with most TEAEs being of mild to moderate severity and consistent with the oxybate safety profile. By week 4, no TEAEs were reported by ≥3% of participants, suggesting resolution of many TEAEs during titration. Participants successfully switched to ON-SXB from their nearest or equivalent prior total nightly TN-OXB dose. Avadel Pharmaceuticals
OBJECTIVES:Measuring disease severity in persons with severe dementia is essential for clinical care and research. Most instruments encounter issues, for example floor effects in characterising persons with severe dementia. We aimed to evaluate the psychometric properties of the Bedford Alzheimer Nursing-Severity Scale (BANS) and its short version, BANS-6, in community-dwelling persons with severe dementia. METHODS:We used baseline data from a multi-centre prospective longitudinal study. 215 caregivers of community-dwelling persons with severe dementia (≥ FAST stage 6c) were recruited (mean age 83.6 ± 8.2). We evaluated BANS' construct validity with exploratory factor analysis, correlation with other established measures, and predictive validity. RESULTS:Factor analysis revealed a two-factor solution (variance 58.35%) with item-2 (sleep-wake cycle) not loading onto any factor. Dropping item-2 (BANS-6) revealed a single-factor solution (variance 49.26%) and Cronbach's α improved from 0.701 to 0.782. FAST did not correlate with the Cohen-Mansfield Agitation Inventory and Quality of Life in Late-Stage Dementia Scale, but both BANS and BANS-6 did. For predictive validity, after adjusting for age, sex and comorbidities, BANS-6 remained significantly associated with key clinical complications of severe dementia: pneumonia (β = 2.09, 95% CI = 0.13-4.05), fever episodes (β = 1.24, 95% CI = 0.10-2.40) and oral antibiotic use (β = 1.33, 95%CI = 0.11-2.55), tube feeding (β = 4.42, 95% CI = 2.62-6.22), pressure sores (β = 2.51, 95% CI = 0.85-4.18), eating problems (β = 3.27, 95%CI = 2.20-4.34), and malnutrition (β = 1.63, 95% CI = 0.24-3.02) in the last 4 months. BANS was not significantly associated with pneumonia, oral antibiotics, and pressure sores, and FAST was not significantly associated with any outcome. CONCLUSIONS:BANS and its short version, BANS-6, are valid, reliable, and clinically relevant tools for assessing dementia severity in community-dwelling persons with severe dementia, warranting further exploration in diverse population settings. The findings suggest that BANS-6 has better psychometrics and clinical utility than BANS.
In the phase 3 REST-ON clinical trial, extended-release, once-nightly sodium oxybate (ON-SXB) demonstrated a safety profile consistent with the known oxybate safety profile, with adverse drug reactions (ADRs) primarily related to tolerability. The long-term safety and tolerability of ON-SXB were investigated in the open-label/switch study RESTORE (NCT04451668). Participants in RESTORE were ≥16 years of age with narcolepsy type 1 or 2 who had completed the REST-ON trial (without starting another oxybate), were on immediate-release twice-nightly SXB (TN-SXB) for ≥1 month, or were oxybate naive. For participants who completed REST-ON but had not initiated TN-SXB or who were oxybate naive, ON-SXB was initiated at 4.5 g/night and increased weekly by 1.5 g/night as needed up to 9 g/night during a 1- to 2-month titration period. Participants then received ON-SXB until they could be transitioned to commercial therapy. This analysis included data from participants who completed REST-ON (without starting another oxybate) or who were oxybate naive and received ≥1 dose of ON-SXB (safety population). Safety data are reported as treatment-emergent adverse events (TEAEs; ie, any AE that occurs during treatment) and ADRs (ie, TEAEs considered drug-related). Of the 50 participants (mean age, 33 years; female, 60%; white, 80%; mean [range] ON-SXB treatment, 408.1 [8–1098] days) who were from REST-ON (n=15) or were oxybate naive (n=35), 76% (38/50) reported ≥1 TEAE; most were mild (n=18; 36%) or moderate (n=18; 36%) in severity. TEAEs occurring in ≥10% of participants included nausea (26%), COVID-19 (12%), somnolence (12%), dizziness (10%), vomiting (10%), sinusitis (10%), and tremor (10%). One (2%) participant reported ≥1 serious AE considered related to ON-SXB treatment (anxiety, delusional thoughts) that led to ON-SXB discontinuation. ADRs were reported by 56% (28/50) of participants. ADRs occurring in ≥10% of participants included nausea (24%), somnolence (12%), and dizziness (10%). Seven (14%) participants experienced ≥1 ADR that led to ON-SXB discontinuation; only nausea led to discontinuation in >1 participant (n=2). These data from RESTORE demonstrate that REST-ON and oxybate-naive participants tolerated ON-SXB well, as TEAEs were primarily mild/moderate in severity. ADRs were aligned with the known safety profile of TN-SXB. Avadel Pharmaceuticals
